AstraZeneca RA drug logs unimpressive PHIII results

AstraZeneca's Phase III pipeline progress took a blow Friday when the company announced that RA candidate fostamatinib failed to show “statistically significant difference in mTSS compared to placebo at 24 weeks.” The measurement, mTSS, means x-rays failed to show the desired results, missing one of two trial goals. The oral SYK inhibitor did hit one target, which was a “significant improvement in ACR20 response rate at 24 weeks.” ACR20 is shorthand for the American College of Rheumatology's Criteria of a 20% improvement.

This is not the first time the drug has met one endpoint only to miss another. The company reported in December that Phase IIb studies comparing fostamatinib's results among RA patients who had not used disease modifying anti-rheumatic drugs or had an inadequate DMARD response showed superiority over placebo at six weeks, but was inferior to adalimumab monotherapy. Adalimumab—AKA AbbVie's blockbuster drug Humira—saw $4.4 billion in US sales last year.

Despite the drumbeat of suboptimal results, AstraZeneca said the drug will remain in the pipeline mix, and is awaiting additional Phase III results for the RA indication. The company expects these results in the second half of 2013.

Fostamatinib was the only Phase III RA drug in the company's pipeline as of December 2012 and its Phase II RA pipeline was equally shallow, consisting of monoclonal antibody mavrilimumab.

ISI analyst Mark Schoenebaum wrote Friday that the RA market will be tough one for oral fostamatinib for two key reasons: it scored lower than Pfizer's JAK inhibitor Xeljanz on its ACR20 scores which “are the single most important data point for doctors treating RA,” and it also fell behind Xeljanz on the radiographic mTSS tests. Schoenebaum added that he expects JAK inhibitors to “be the dominant oral class to treat RA” and an approved fostamatinib would be shunted to secondary treatment status.